Rasmussen encephalitis and comorbid autoimmune diseases: A window into disease mechanism?

OBJECTIVE: To describe a potential association between comorbid autoimmune disease and Rasmussen encephalitis (RE) and discuss potential insights into underlying RE pathogenesis. METHODS: We report a case series of 4 patients with RE in whom a comorbid autoimmune disease was subsequently diagnosed and review the literature on possible common susceptibility factors. RESULTS: In 4 patients who presented with typical clinical features of RE, a comorbid autoimmune disease was subsequently diagnosed: Hashimoto thyroiditis, ulcerative colitis, Crohn disease, and systemic lupus erythematosus. We discuss the possible common predisposing factors. CONCLUSIONS: The association of RE, a rare entity, with a comorbid autoimmune disease raises the possibility of shared mechanisms of susceptibility, including common immunogenetic and/or environmental risk factors.

Prevalence of neurologic autoantibodies in cohorts of patients with new and established epilepsy.

PURPOSE: Autoantibodies to specific neurologic proteins are associated with subacute onset encephalopathies, which often present with seizures that are poorly controlled by conventional antiepileptic drugs (AEDs). Previous cross-sectional studies have found specific neurologic antibodies in a small proportion of people with established epilepsy, but these investigations have seldom included patients with recent diagnosis. METHODS: We screened two large epilepsy cohorts to investigate the prevalence of multiple autoantibodies in adult patients with either established or newly diagnosed, untreated epilepsy. KEY FINDINGS: Eleven percent of patients had antibodies to one or more antigen: voltage-gated potassium channel (VGKC) complex proteins (5%), glycine receptors (3%), and glutamic acid decarboxylase (GAD) and N-methyl-D-aspartate (NMDA) receptors (1.7% each). There was no difference in the prevalence of antibodies, individually or collectively, between patients with established and newly diagnosed epilepsy or with generalized or focal epilepsy. There was, however, a significantly higher prevalence of positive antibody titers in patients with focal epilepsy of unknown cause than in those with structural/metabolic focal epilepsy (14.8% vs. 6.3%; p < 0.02). Newly diagnosed antibody-positive patients were less likely to achieve adequate seizure control with initial treatment than antibody-negative patients, but this difference failed to reach statistical significance. SIGNIFICANCE: The presence of autoantibodies is equally common in newly diagnosed and established epilepsy, it is therefore unlikely to be an epiphenomenon of long-standing refractory seizures.

Epilepsy after subarachnoid hemorrhage: the frequency of seizures after clip occlusion or coil embolization of a ruptured cerebral aneurysm: results from the International Subarachnoid Aneurysm Trial.

OBJECT: The aim of this study was to determine the probability of seizures after treatment of a ruptured cerebral aneurysm by clip occlusion and coil embolization, and to identify the risks and predictors of seizures over the short- and long-term follow-up period. METHODS: The study population included 2143 patients with ruptured intracranial aneurysms who were enrolled in 43 centers and randomly assigned to clip application or coil placement. Those patients suffering a seizure were identified prospectively at various time points after randomization, as follows: before treatment; after treatment and before discharge; after discharge to 1 year; and annually thereafter. RESULTS: Two hundred thirty-five (10.9%) of the 2143 patients suffered a seizure after randomization; 89 (8.3%) of 1073 and 146 (13.6%) of 1070 in the endovascular and neurosurgical allocations, respectively (p = 0.014). In 19 patients the seizure was associated with a rehemorrhage. Of those patients who underwent coil placement alone, without additional procedures, 52 suffered a seizure, and in the group with clip occlusion alone, 91 patients suffered a seizure. The risk of a seizure after discharge in the endovascular group was 3.3% at 1 year and 6.4% at 5 years. In the neurosurgical group it was 5.2% at 1 year and 9.6% at 5 years. The risk of seizure was significantly greater in the neurosurgical group at both 2 years and at up to 14 years (p = 0.005 and p = 0.013, respectively). The significant predictors of increased risk were as follows: neurosurgical treatment allocation, hazard ratio (HR) 1.64 (95% CI 1.19-2.26); younger age, HR 1.54 (95% CI 1.14-2.13); Fisher grade > 1 on CT scans, HR 1.34 (95% CI 0.62-2.87); delayed ischemic neurological deficit due to vasospasm, HR 2.10 (95% CI 1.49-2.94); and thromboembolic complication, HR 5.08 (95% CI 3.00-8.61). A middle cerebral artery (MCA) aneurysm location was also a significant predictor of increased risk in both groups; the HR was 2.23 (95% CI 1.57-3.17), with the probability of seizure at 6.1% and 11.5% at 1 year in the endovascular and neurosurgery groups, respectively. CONCLUSIONS: The risk of seizures after coil embolization is significantly lower than that after clip occlusion. An MCA aneurysm location increased the risk of seizures in both groups.

Epilepsy and the subsequent risk of cerebral tumour: record linkage retrospective cohort study.

BACKGROUND: Studies suggest that seizures may precede the detection of cerebral tumour by several years. Aim To quantify the risk of cerebral tumour after new onset seizures, with particular interest in long term risk. METHODS: Using the Oxford Record Linkage Study (ORLS, 1963-1998) and English national linked Hospital Episode Statistics (1999-2005), cohorts of people with a first admission for epilepsy were constructed. Subsequent admissions with cerebral tumour were identified. The rate of occurrence of subsequent cerebral tumour in each epilepsy cohort was compared with that in a comparison cohort and expressed as a rate ratio (RR). RESULTS: The RR for cerebral tumour after epilepsy, relative to the rate of cerebral tumour in the comparison cohort, was 19.9 (95% CI 17.2 to 22.9) in the ORLS cohort and 19.7 (18.3-21.1) in the England cohort. The RR for malignant tumours were, respectively, 25.6 (21.7 to 30.0) and 27.3 (25.2 to 29.6). The RR for benign tumours were 10.1 (7.38 to 13.6) and 10.4 (9.07 to 11.8), respectively. The risk was highest for those aged 15-44 years at initial admission for epilepsy both in Oxford (24.2, 18.5 to 31.5) and England (38.1, 32.8 to 44.2). The risk of cerebral tumour was still raised several years after initial admission for epilepsy: in the ORLS cohort at 15 years or more, the RR was 3.29 (1.39 to 6.66) and, in the England cohort 5-7 years after initial admission, the RR was 5.27 (3.87 to 7.06). CONCLUSIONS: Seizures may herald the development of cerebral tumour, remote in time as well as soon after onset, with implications for guidelines on continued surveillance of those with new onset seizures.

Functional and structural changes in the memory network associated with left temporal lobe epilepsy.

Understanding functional plasticity in memory networks associated with temporal lobe epilepsy (TLE) is central to predicting memory decline following surgery. However, the extent of functional reorganization within memory networks remains unclear. In this preliminary study, we used novel analysis methods assessing network-level changes across the brain during memory task performance in patients with TLE to test the hypothesis that hippocampal functions may not readily shift between hemispheres, but instead may show altered intra-hemispheric organization with unilateral damage. In addition, we wished to relate functional differences to structural changes along specific fibre pathways associated with memory function. Nine pre-operative patients with intractable left TLE and 10 healthy controls underwent functional MRI during complex scene encoding. Diffusion tensor imaging was additionally performed in the same patients. In our study, we found no evidence of inter-hemispheric shifts in memory-related activity in TLE using standard general linear model analysis. However, tensor independent component analysis revealed significant reductions in functional connectivity between bilateral MTL, occipital and left orbitofrontal regions among others in left TLE. This altered orbitofrontal activity was directly related to measures of fornix tract coherence in patients (P < 0.05). Our results suggest that specific fibre pathways, potentially affected by MTL neurodegeneration, may play a central role in functional plasticity in TLE and highlight the importance of network-based analysis approaches. Relative to standard model-based methods, novel objective functional connectivity analyses may offer improved sensitivity to subtle changes in the distribution of memory functions relevant for surgical planning in TLE.

Rasmussen's encephalitis.

Rasmussen's encephalitis, a syndrome characteristically present-ing in children with the onset of partial motor seizures followed by progressive hemiparesis and cognitive impairment, and accompanied by unilateral cerebral atrophy, was described nearly 50 years ago, yet the cause and optimum treatment remain unclear. Although it was originally presumed to have a viral aetiology, the possible roles of antibody-mediated mechanisms and more recently cell-mediated immunity in its pathogenesis have come under increasing scrutiny in the last ten years. These developments are discussed, together with a review of the clinical features. The advances in treatment which have accompanied these changes are also assessed.

Levetiracetam: an innovative and cost-effective add-on drug for refractory partial epilepsy.

Poorly-controlled epilepsy can have a significant negative impact on quality of life, clinically important changes are seen in patients emotional well-being, cognitive functioning, social functioning and energy/fatigue levels. Poorly-controlled epilepsy places an undue economic burden on the patient and community. Increased costs are seen in both direct and indirect healthcare costs (e.g., inpatient care and loss of earnings associated with time lost from work). Therefore, long-term efficacy and tolerability are key considerations when designing the patient's treatment regimen. Therapy can be individualized using both classical drugs and newer antiepileptics such as levetiracetam (Keppra, UCB Pharma Inc.), which is currently recommended as add-on therapy for partial-onset seizures. Studies have revealed characteristics that suggest levetiracetam is the first of a new class of antiepileptic drugs, differentiated by its innovative mechanism of action. Its efficacy and tolerability have enabled many patients who were refractory to treatment with other antiepileptic drugs to achieve long-term seizure freedom. Levetiracetam has a high long-term retention rate, a powerful measure of adverse events and efficacy over time. Another equally important benefit is ease of use, levetiracetam is administered twice-daily and has a simple titration regimen. Pharmacoeconomic data show that the incremental cost of treating patients with levetiracetam is low when compared with the benefits of seizure freedom. Ongoing studies suggest that this antiepileptic drug has potential as first-line treatment for many types of epilepsy and in many different patient populations.